Monday, January 28, 2013

What do Dead Bodies, Nematodes, and a former Oregon State Beavers Pitcher Have in Common?

by Ellen Mintz

Believe
it or not, these three seemingly unrelated organisms have each undergone a
process that is incredibly significant in medical history and current scientific
research.To really answer that
question though, we need to take a closer look at the most significant and
important organ in our body: the brain.

The
brain, along with the spinal cord, comprises the central nervous system. As its
name implies, this is the command center of all of the activity that keeps our
bodies alive, aware, and functioning.The brain controls crucial processes like breathing, digesting, and
waking up in the morning. Stimuli from the environment around us send messages through
our bodies in the form of electrical signals.Neurons are the cells that transmit these signals,
communicating from cell to cell through the release of tiny chemicals called
neurotransmitters.Upon reaching
the central nervous system, these signals are processed and delivered as electrical
impulses to effectors such as skeletal muscle and digestive organs.

In
addition to movement, the brain controls emotions and feelings.These arise from increased activity in
different parts of the brain (check out the map below!).Regions including the amygdala, frontal
cortex, hypothalamus, and cerebral cortex can all lead to feelings of sadness
and depression.

Brain Anatomy

Many
tissues around the body such as the skin, are quick to repair themselves
following damage from injury or the natural process of aging through the use of
unspecialized stem cells that then differentiate into the needed cell
type.The central nervous system,
however, is notoriously difficult to repair and was believed to have no source
of stem cells. In 1998, scientists discovered cells in the hippocampus that
were able to become new neurons, and subsequent discoveries of more of these
cells led to the hope that conditions such as paralysis that are often the
result of traumatic brain injury could be treated.This has of yet not been proven to be completely successful.

Fluorescence image of a neural stem cell

It
has taken centuries to accumulate all of the knowledge that we have today about
the brain.Starting in the late
1700s and into 1800s, research in neurobiology and of the electrical impulses
in the nervous system made huge strides.It
was during this time that scientists discovered that muscles and nerves were
excited by electrical signals.This revelation was demonstrated by applying electric currents to the
bodies of cadavers (dead bodies, anyone?!), resulting in macabre post-death
movements sure to excite any pre-movie era horror enthusiasts. Eventually, this
led to the discovery by Italian scientist Luigi Rolando in 1809 that the brain
responded to electrical pulses also.

It
took another 50 years for scientists to develop the knowledge and instruments
to be able to apply this knowledge of the electrical conduction of the central
nervous system directly to the organs themselves, and use electricity to control
different levels stimulation as a method for investigating brain function.First in animals like dogs and monkeys,
and much later in humans, electrical stimulation of the brain provided
knowledge the physiology of this organ.When this was then applied to the treatment of different disease
conditions, particularly mental illness, the fun really began!

What ECT actually looks like!

One
of the first methods of electrical brain stimulation to treat depression and personality
and mood disorders was electroshock therapy, now called electroconvulsive
therapy, or ECT. The idea behind electroconvulsive therapy is to cause a huge
storm of electrical activity in different parts of the brain.This invokes a small seizure in the
patient and resets electrical pathways and brain chemistry.While often seen fictionalized in
popular media as a painful, bone jarring and maniacal spasms, it is in reality
done under anesthesia and can be successful when other treatments have failed.

NOT an accurate representation of ECT!

In
1985, a procedure called transcranial magnetic stimulation, or TMS, was
introduced as a less invasive and intense method of mood adjustment and
depression treatment and approved for use on humans in 2009. This technique
involves placing electromagnetic coils near the skull to deliver quick magnetic
pulses to the brain, increasing the firing of neurons in mood associated brain
regions.There is a decrease in
the risk of inducing a seizure using this procedure, making it safer and
applicable to a wider range of patients than traditional ECT.

C. elegans

Taking
the idea of magnetic stimulation multiple steps further, a physicist at SUNY Buffalo, Dr. Arnd Pralle, utilized magnetic
fields to heat up nanoparticles placed in neurons in the brain.These particles activate temperature
sensitive ion channels in the cells, causing them to react and potentially stimulate
positive changes in neuron firing patterns. Although this method has yet to be
tested in human brains, it has been shown to cause Caenorhabditis elegans, a nematode used as a model organism in
developmental biology and neurology (a test subject like the dead bodies of
earlier…), to change what direction they were moving in. Dr. Pralle and his
collaborators are currently investigating using genes from bacteria that are known
to make magnetic nanoparticles and integrating them into humans using a viral
therapy, in addition to other biocompatible delivery methods.Ultimately, this technique would be
able to elucidate neuronal circuits in the brain by allowing stimulation of different
regions controlling mood and behavior, and could be used as a research tool to
study conditions such Parkinson’s disease and traumatic brain injury that
resulted from dysfunctional or impaired neurons.

The
spinal cord has also been subjected to electrical stimulation as well, however
not for the same purposes as the brain.Electrical stimulation of the spinal cord has been investigated as a way
to improve limb function and health, focusing on patients with spinal cords or
body parts that have been damaged by accidents or debilitating diseases.Because the spinal cord transmits
electrical signals and impulses from the brain and reflex neurons to muscles
and organs around the body, damage can result in loss of movement and control,
lack of sensation to stimuli including pain, temperature and touch, and reduced
to nonexistent function in crucial organs and systems including the heart,
lungs, digestive, and reproductive systems. It has been shown however that rats with implanted electrodes in
their spinal cord regain minor leg function when placed on a treadmill, and
eventually are able to walk on their own. Brief periods of epidural spinal cord electrical stimulation
was shown to relieve pain, result in skin ulcer healing, and increase circulation
in patients suffering from limb-threatening ischemia.

Still
curious about how baseball fits into this topic? In 2006, Rob Summers, a
pitcher for Oregon State, was paralyzed from the neck down in a tragic hit and
run accident, ending his baseball career.Intense rehabilitation and therapy improved his upper body movement and
he eventually regained the use of his arms.In 2009, he sought out the help of Dr. V. Reggie Edgerton, a
professor and neurobiologist at UCLA who had previously led spinal cord studies
on electrical stimulation in rats.Dr. Edgerton and his collaborators implanted electrodes in the lower
sections of Summers’ spinal cord and through electrical stimulation, were able
to temporarily reactive the neural networks in his spinal cord.Summers was able to move his legs while
on a treadmill with upper body support, briefly stand on his own, and also
experienced huge improvements in blood pressure, bladder and sexual function,
and temperature regulation.

All
of these therapies involving electromagnetic activity and the central nervous
system to treat depression and other diseases and pathologies have many
benefits and are good starting points for the development of safer and less
invasive procedures.Further
applications of these concepts could provide longer, healthier, and happier
outlooks to those suffering from paralysis, depression, and neural diseases
like Parkinson’s.In structures as
multifaceted and complex as the brain and spinal cord, it is anyone’s best
guess as to from where the next discovery will come!

3 comments:

That pitchers story is really sad but inspirational. I imagine those electrodes that were implanted in him jump starting his spinal cord nerves like a car battery. I'm not sure how correct that analogy is but this is really awesome stuff!

I love your blog title! Very interesting stuff. Does the electrical stimulation actually induce the stem cells to become new neurons? Or is the stimulation simply helping already existing neurons to fire?